This invention relates to the use of certain quinazoline compounds in the treatment of polycystic kidney disease.
Polycystic Kidney Disease occurs in two forms; autosomal recessive (ARPKD) and autosomal dominant (ADPKD). The two forms of the disease have distinct genetic bases and two genes causing ADPKD have been identified while those of ARPKD have not. The manifestations of the disease are however very similar. Both result from a hyperproliferation of tubule epithelial cells that ultimately results in destruction of tubular structure with cyst formation leading to chronic renal failure. The reason for cyst formation is becoming more clear, in that, there is good evidence that the level of growth factors EGF/TGF.alpha. (these two growth factors share the same cellular receptor) are greatly increased in the cyst fluid in these lesions. In addition, it has been noted both the ARPKD and ADPKD that the EGF receptor is mislocated, being present on the luminal surface near the cyst fluid as opposed to the basolateral region as in normal tubular epithelial cells. It has also been shown that TGF.alpha. and EGF induce cysts in renal tissues in vitro. In addition, TGF.alpha. overexpression in transgenic mice is cystogenic in vivo, that is, animals that have a constitutive overexpression of TGF.alpha. will develop kidney cysts. Furthermore, renal cyst fluid contains EGR and EGF like peptides in mitogenic concentrations and finally cystic renal tissue has increased TGF.alpha. expression.